Single-cell transcriptomic data reveal the cellular heterogeneity of glutamine metabolism in gastric premalignant lesions and early gastric cancer

• • Single-cell atlas of 22,511 cells from CAG and EGC lesions reveals epithelial cells as the dominant population, with glutamine metabolism activity significantly higher in EGC epithelial cells than in CAG (p < 0.01), indicating a metabolic shift during early malignant transformation that could serve as a diagnostic threshold for early intervention. • • Epithelial subpopulation cluster_4 exhibits elevated glutamine metabolism in EGC compared to CAG, and its marker gene ERO1LB is overexpressed in human GC tissue lesions, providing a potential therapeutic target with clinical relevance for GC prevention and treatment. • • Overexpression of ERO1LB in GC cells increases glutamine metabolism, facilitates cell growth and migration, and prevents apoptosis, while targeted suppression reverses these effects, demonstrating a causal role in GC progression and suggesting that ERO1LB inhibition could reduce tumor growth by attenuating glutamine metabolism. • • The study identifies ERO1LB as a key orchestrator of glutamine metabolism in GC, with experimental validation showing that its modulation directly impacts malignant phenotypes, offering a novel target for developing early intervention regimens and improving understanding of GC pathogenesis.